China’s Zhejiang Huahai Pharmaceutical set off a global recall after it informed global regulators last month that it had discovered the suspected cancer-causing impurity N-nitrosodimethylamine in its valsartan API after changing its manufacturing process. But the FDA is now reporting that the tainted ingredient may have been on the market for years, not weeks or months.
The FDA said in its most recent update that it wanted to “put some context around the actual potential risk posed to patients” from the levels of N-nitrosodimethylamine (NDMA) found in the products.
“Based on records from the manufacturer of the recalled valsartan, some levels of the impurity may have been in the valsartan-containing products for as long as four years.”
It said FDA scientists estimate that if 8,000 people took the highest valsartan dose (320 mg) from the recalled batches every day for the full four years, there may be one additional case of cancer over the lifetimes of those 8,000 people. "This assessment led to FDA’s decision to have these batches recalled," the agency said.
China’s Zhejiang Huahai Pharmaceutical last month reported that after making its discovery it had suspended manufacturing and supply of valsartan, sealed its unshipped batches and informed customers and regulators, including the FDA. It said that while no regulatory agency has currently placed restrictions on NDMA, it was working with regulators to set an industry standard on NDMA. With a reported 45% market share, the Huahai API turned up in many generic products.
Developed by Novartis and initially sold as Diovan, the high blood pressure and heart failure drug is now off patent and is used in many medicines made by many drugmakers. Novartis still markets Diovan and other branded valsartan-containing drugs like Exforge and Entresto while Teva’s Actavis, Stada and Dexcel Pharma are among others selling generics of the drug. Novartis in a statement said its branded products and those made for the U.S. are unaffected but that it is recalling Sandoz's valsartan and valsartan HCT distributed in 23 countries.
Novartis also said “the amount of NDMA found in valsartan API is neither considered to represent a significantly increased risk to patients taking Sandoz valsartan or Sandoz valsartan HCT film coated tablets nor having an effect on the efficacy of the product.” The FDA in its evaluation said that the amount of NDMA in the products being recalled exceed limits that the Environmental Protection Agency deems safe.
The report comes as two more Chinese companies have stepped forward to say they are recalling blood pressure meds tainted with NDMA. Zhejiang Tianyu Pharmaceutical and Zhuhai Rundu Pharmaceutical reported the recalls to the Shenzhen stock exchange, according to the Asia Times, which didn’t say if they were producing affected APIs or just finished products that had used the affected APIs.
It said they had shipped products to Taiwan but neither appear on the FDA’s list of a dozen brands that are being recalled in the U.S. The agency also has a list of products not affected by the recall.